The overall goal of this Program Project grant application is to elucidate the mechanisms of autoimmunity to type V collagen in heart and lung transplants. The use of animal models to study mechanism is essential for advancing our understanding of this important clinical problem. To this end, the focus of the Transgenic Mouse Core (Core B) is to provide the technical expertise for the generation of genetically modified mouse strains and to maintain a colony of these unique mouse strains such that mice are generated for the experiments that address the aims of the proposed three Projects. To do so, the first part of Core B will utilize personnel in the University of Wisconsin Biotechnology Center's (UWBC) Transgenic Animal Facility (TAF) to (1) carry out gene targeting experiments in embryonic stem cells to produce ES cell clones with genetically altered alleles and the blastocyst microinjections to generate new mouse mutant strains carrying these mutant alleles, (2) to rederive genetically modified strains that are obtained from other institutions or are housed presently in non-SPF animal facilities so that the mouse stocks for this project can be housed in a newly opened specific pathogen free vivarium at the University of Wisconsin, and (3) cryopreserve for long term storage and safe keeping all the genetically modified mouse strains used in this proposal. In the second part of Core B, Core staff will (1) verify the genetic identity of all the mutant mouse strains rederived for the projects and the inducible tissue specific expression of certain strains, (2) maintain a breeding colony of all the genetically modified mouse strains such that the required numbers of the mouse stocks can be supplied to the individual Projects as needed for their experimentation. This Core will provide specific services for each of the three projects in this proposal. The services provided by this Core will be essential for achieving the overall goals of this grant application.